Treatment-related adverse effects with TKIs in patients with advanced or radioiodine refractory differentiated thyroid carcinoma: a systematic review and meta-analysis

Figures & data

Table S1 Baseline characteristics of enrolled studies

Study	Year	Treatment	Number of patients evaluated for toxicity	Number of patients experienced toxicity (grade ≥3)/all grade
				Hand-foot syndrome	Weight loss	Diarrhea	Rash	Mucositis	Hypocalcemia	Hyper tension	Nausea	Fatigue	Anorexia	Voice change	Vomiting	Increased ALT	Increasing AST
Schneider et al^Citation1	2012	Sorafenib	31	7/22	3/18	2/16	5/17	3/16	0/15	5/15	0/3	NA	NA	NA	NA	NA	NA
Brose et al^Citation2	2014	Sorafenib	207	42/158	0/97	12/142	10/104	2/48	19/39	20/84	0/43	12/103	5/66	1/25	1/23	6/26	2/23
Cabanillas et al^Citation3	2015	Lenvatinib	58	NA	7/40	6/39	NA	1/18	NA	6/44	0/29	5/35	1/30	0/25	0/22	NA	NA
Schlumberger et al^Citation4	2015	Lenvatinib	261	9/83	25/121	21/155	1/42	11/93	7/18	109/177	6/107	24/154	12/131	3/63	5/74	0/1	0/1
Berdelou et al^Citation5	2017	Lenvatinib	75	0/21	0/44	1/34	NA	2/18	NA	26/50	0/14	6/46	1/27	0/1	0/5	NA	NA
Nervo et al^Citation6	2018	Lenvatinib	12	2/11	2/11	5/8	NA	1/7	NA	5/9	1/9	1/7	NA	0/3	1/4	NA	NA
Balmelli et al^Citation7	2018	Lenvatinib	13	0/1	NA	2/4	NA	1/4	NA	1/2	NA	2/6	1/3	0/1	NA	NA	NA

Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; NA, not available.

Table S2 Risk of bias in enrolled studies

Study	Adequate sequence generation	Allocation concealment	Blinding	Incomplete outcome data addressed	Free selective reporting	Free of other bias
Schneider et al^Citation1	Yes	No	Yes	No	No	No
Brose et al^Citation2	Yes	Yes	Yes	No	No	No
Cabanillas et al^Citation3	Yes	No	Yes	No	No	No
Schlumberger et al^Citation4	Yes	Yes	Yes	No	No	No
Berdelou et al^Citation5	Yes	No	No	No	No	No
Nervo et al^Citation6	Yes	No	No	No	No	No
Balmelli et al^Citation7	Yes	No	No	No	No	No

Figure 1 Flow chart of the selection of studies included in this pooled study.

Figure 2 Frequency of all grade toxicity, including hand-foot syndrome (A), hypocalcemia (B), rash (C), voice change (D), hypertension (E), nausea (F), elevated ALT (G), elevated AST (H), and vomiting (I), among sorafenib and lenvatinib.

Note: ****P<0.0001 indicates statistical significance.

Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase.

Figure 3 Frequency of grade ≥3 AEs, including hand-foot syndrome (A), weight loss (B), hypocalcemia (C), hypertension (D), nausea (E), and elevated ALT (F), among sorafenib and lenvatinib.

Note: *P<0.05, **P<0.01, ***P<0.001, ****P<0.0001 indicate statistical significance.

Abbreviations: AEs, adverse effects; ALT, alanine aminotransferase.

Figure S1 Risk of bias graph.

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